Efficiency of antisense oligonucleotide drug discovery.

C. Bennett
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引用次数: 33

Abstract

The costs for discovering and developing new drugs continue to escalate, with current estimates that the average cost is more than $800 million for each new drug brought to the market. Pharmaceutical companies are under enormous pressure to increase their efficiency for bringing new drugs to the market by third-party payers, shareholders, and their patients, and at the same time regulators are placing increased demands on the industry. To be successful in the future, pharmaceutical companies must change how they discover and develop new drugs. So far, new technologies have done little to increase overall efficiency of the industry and have added additional costs. Platform technologies such as monoclonal antibodies and antisense oligonucleotides have the potential of reducing costs for discovery of new drugs, in that many of the steps required for traditional small molecules can be skipped or streamlined. Additionally the success of identifying a drug candidate is much higher with platform technologies compared to small molecule drugs. This review will highlight some of the efficiencies of antisense oligonucleotide drug discovery compared to traditional drugs and will point out some of the current limitations of the technology.
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反义寡核苷酸药物的发现效率。
发现和开发新药的成本继续上升,目前估计,每一种新药推向市场的平均成本超过8亿美元。制药公司面临着巨大的压力,要提高第三方付款人、股东及其患者将新药推向市场的效率,与此同时,监管机构对该行业提出了越来越高的要求。为了在未来取得成功,制药公司必须改变他们发现和开发新药的方式。到目前为止,新技术对提高整个行业的效率收效甚微,而且还增加了额外的成本。单克隆抗体和反义寡核苷酸等平台技术具有降低新药发现成本的潜力,因为传统小分子所需的许多步骤可以跳过或简化。此外,与小分子药物相比,平台技术识别候选药物的成功率要高得多。本文将重点介绍反义寡核苷酸药物发现与传统药物相比的一些效率,并指出目前该技术的一些局限性。
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Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Delivery of antisense oligonucleotide to the cornea by iontophoresis. Rapid identification of antisense mRNA-expressing clones using strand-specific RT-PCR. Analysis of a mitochondrial apoptotic pathway using Bid-targeted ribozymes in human MCF7 cells in the absence of a caspase-3-dependent pathway. HIV Tat peptide enhances cellular delivery of antisense morpholino oligomers.
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